APOE and Alzheimer disease: The major genetic risk factor for late-onset Alzheimer’s disease is the apolipoprotein E (APOE) gene, with the ɛ4 allele increasing risk of dementia12,13 and the ɛ2 allele decreasing risk.14,15 Multiple additional genetic loci have been identified in genome-wide association studies (GWAS)16 to increase late-onset Alzheimer’s disease-dementia risk, though to a smaller degree than APOE-ɛ4.